Regulation of ectopic trypsin and proinflammatory cytokine expression by NF-κB and AP-1 in influenza A virus induced myocarditis
10.3969/j.issn.1000-4718.2015.05.004
- VernacularTitle:NF-κB 和 AP-1对 A 型流感病毒性心肌炎组织中异位胰蛋白酶及促炎细胞因子表达的调控
- Author:
Haiyan PAN
;
Lujing XUE
;
Yiping WANG
;
Huamei SUN
;
Min PAN
- Publication Type:Journal Article
- Keywords:
Influenza A virus;
Viral myocarditis;
Nuclear factor-κB;
Activator protein-1;
Trypsin
- From:
Chinese Journal of Pathophysiology
2015;(5):791-796
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the regulatory effects of nuclear factor-κB ( NF-κB) and activator protein-1 (AP-1) on the expression of ectopic trypsin and proinflammatory cytokines in influenza A virus (IAV)-induced myocardi-tis.METHODS:Male BALB/c mice of 8 weeks old ( n=40) were randomly divided into 4 groups:normal control group ( NC) , infection control group ( IC) , NF-κB inhibitor group ( NI) and AP-1 inhibitor group ( AI) .The mice in NC group and IC group were instilled intranasally with 15μL saline and 40 plaque forming units ( PFU) IAV, respectively.The mice in NI group and AI group were infected intranasally with 40 PFU IAV and injected intraperitoneally with 10 mg/kg NF-κB inhibitor pyrrolidine dithiocarbamate ( PDTC) or 2.5 mg/kg AP-1 inhibitor nordihydroguaiaretic acid ( NDGA) once daily. The mice were euthanized at day 9 after instillation, and the hearts were removed for pathological and biochemical analysis. RESULTS:IAV infection induced significant up-regulation of ectopic trypsin, and proinflammatory cytokines interleukin 6 (IL-6), IL-1βand tumor necrosis factor-α(TNF-α) in the myocardium, and triggered acute myocarditis.PDTC signifi-cantly inhibited NF-κB activation and up-regulation of ectopic trypsin and proinflammatory cytokines, and effectively sup-pressed IAV replication and myocardial inflammatory response (P<0.01).NDGA effectively inhibited AP-1 activity (P<0.01) and mildly suppressed up-regulation of proinflammatory cytokines ( P<0.05) , but had no effects on the expression of ectopic trypsin, IAV replication and the extent of myocarditis ( P>0.05) .CONCLUSION:IAV infection induces up-regulation of ectopic trypsin and proinflammatory cytokines in myocardium predominantly by the activation of NF-κB.AP-1 signaling pathway might be only partially involved in the regulation of proinflammatory cytokines.
